Copper-catalyzed cyanation of aryl iodide with the combined cyanide source of urea and DMSO

A simple copper-catalyzed cyanation of aryl iodide with the combination of urea and dimethyl sulfoxide as a cyanide source is achieved, providing nitriles in moderate to good yields. This new approach represents an exceedingly practical and safe method for the synthesis of aryl nitriles.     

Copper-mediated cyanation of aryl halide with the combined cyanide source

A simple copper-mediated cyanation of aryl halide with the combination of ammonium bicarbonate and N,N-dimethylformamide as a cyanide source is achieved, providing nitriles in moderate to good yields. This new approach represents an exceedingly practical and safe method for the synthesis of aryl nitriles.     

P(i-BuNCH2CH2)3N: an efficient ligand for the direct alpha-arylation of nitriles with aryl bromides

A new catalyst system for the synthesis of alpha-aryl-substituted nitriles is reported. The bicyclic triaminophosphine P(i-BuNCH(2)CH(2))(3)N (1b) serves as an efficient and versatile ligand for the palladium-catalyzed direct alpha-arylation of nitriles with aryl bromides. Using ligand 1b, ethyl cyanoacetate and primary as well as secondary nitriles are efficiently coupled with a wide variety of aryl bromides possessing electron-rich, electron-poor, electron-neutral, and sterically hindered groups.     

Mild palladium-catalyzed selective monoarylation of nitriles

Two new palladium-catalyzed procedures for the arylation of nitriles under less basic conditions than previously reported have been developed. The selective monoarylation of acetonitrile and primary nitriles has been achieved using alpha-silyl nitriles in the presence of ZnF2. This procedure is compatible with a variety of functional groups, including cyano, keto, nitro, and ester groups, on the aryl bromide. The arylation of secondary nitriles occurred in high yield by conducting reactions with zinc cyanoalkyl reagents. These reaction conditions tolerated base-sensitive functional groups, such as ketones and esters. The combination of these two methods, one with alpha-silyl nitriles and one with zinc cyanoalkyl reagents, provides a catalytic route to a variety of benzylic nitriles, which have not only biological significance but utility as synthetic intermediates. The utility of these new coupling reactions has been demonstrated by a synthesis of verapamil, a clinically used drug for the treatment of heart disease, by a three-step route from commercial materials that allows convenient variation of the aryl group.     

Palladium-catalyzed, copper(I)-mediated coupling of boronic acids and benzylthiocyanate. A cyanide-free cyanation of boronic acids

A new method for the synthesis of nitriles is described. As a complement to the classic cyanation of aryl halides using cyanide sources and a transition metal catalyst, the palladium-catalyzed cross-coupling of thiocyanates with boronic acids in the presence of copper(I) thiophene-2-carboxylate (CuTC) affords nitriles in good to excellent yields.     

A green and efficient access to awl nitriles via an electrochemicalanodic oxidation

The nitrile functionality is a key building block in synthetic chemistry, and has wide applications in pharmaceuticals. However, traditional methodologies for the synthesis of nitriles are limited to harsh reaction conditions. Herein, we report a new and efficient access to aryl nitriles by an electrochemical synthesis. Compared with the conventional synthetic methods, this electrochemical synthesis is more environmentally friendly and easier to handle.     

The palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates

A palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates has been developed, providing aryl nitriles in moderate to excellent yields. It represents a facile procedure to access aryl nitriles.     

Copper-mediated cyanation of aryl boronic acids using benzyl cyanide

An efficient copper-mediated synthesis of aryl nitriles from aryl boronic acids has been achieved using benzyl cyanide as a user-friendly cyanide source. Various aryl boronic acids underwent the reaction smoothly, affording the corresponding aryl nitriles in moderate to good yields. tert-Butyl hydroperoxide (TBHP) was found to be a critical agent facilitating the cyanation reaction.     

A green and efficient access to aryl nitriles via an electrochemical anodic oxidation

The nitrile functionality is a key building block in synthetic chemistry, and has wide applications in pharmaceuticals. However, traditional methodologies for the synthesis of nitriles are limited to harsh reaction conditions. Herein, we report a new and efficient access to aryl nitriles by an electrochemical synthesis. Compared with the conventional synthetic methods, this electrochemical synthesis is more environmentally friendly and easier to handle.     

Nickel‐Catalyzed Cyanation of Aryl Chlorides and Triflates Using Butyronitrile: Merging Retro‐hydrocyanation with Cross‐Coupling

We describe a nickel‐catalyzed cyanation reaction of aryl (pseudo)halides that employs butyronitrile as a cyanating reagent instead of highly toxic cyanide salts. A dual catalytic cycle merging retro‐hydrocyanation and cross‐coupling enables the conversion of a broad array of aryl chlorides and aryl/vinyl triflates into their corresponding nitriles. This new reaction provides a strategically distinct approach to the safe preparation of aryl cyanides, which are essential compounds in agrochemistry and medicinal chemistry.     

Cs2CO3 in pyrrolidinone promoted hydration of functionalized (hetero)aryl nitriles under metal-free conditions

An efficient hydration reaction of various (hetero)aryl nitriles using Cs₂CO₃ in pyrrolidinone is described. This new metal-free protocol proved to be highly effective and general to synthesize a variety of (hetero)aryl amides.     

Programming Rapid Functional Group Diversification into a Solid-State Reaction: Aryl Nitriles for Self-Assembly,Click Reactivity,and Discovery of Coexisting Supramolecular Synthons

A method to rapidly diversify the molecules formed in organic crystals is introduced, with aryl nitriles playing a novel dual role as both hydrogen-bond acceptors and modifiable organic groups. The discovery of coexisting supramolecular synthons in the same crystal is also described. The general concept is demonstrated by using a bis(aryl nitrile) alkene that undergoes a hydrogen-bond-directed intermolecular [2+2] photodimerization to form a tetra(aryl nitrile)cyclobutane. The product is readily converted by click reactivity to a tetra(aryl tetrazole) and by hydrolysis to a tetra(aryl carboxylic acid). The integration of aryl nitriles into solid-state reactions opens broad avenues to post-modify products formed in crystalline solids for rapid diversification.     

Acid Catalyzed Multicomponent Reaction to Access Functionalized N-Benzhydryl Amides: A Tandem Ritter Reaction

Acid catalyzed multicomponent reaction (MCR) for the synthesis of N-benzhydryl amide derivatives from aldehydes, N,N-disubstituted arylamines and nitriles is reported. The reaction is compatible with electronically differentiating aryl/heteroaryl aldehydes/acetals, different nucleophiles (cyclic and acyclic N,N-disubstituted arylamines,β-naphthols, 1,3 dicarbonyl, 1,3,5-trimethoxy benzene), alkyl nitriles, aryl/heteroaryl nitriles in catalytic TFA/TfOH through tandem Ritter reaction. The one-pot MCR with broad substrate scope generated a wide variety of sterically hindered N-substituted amides and is successfully applied for the synthesis of isoindolinone.     

A Mild and Efficient Procedure for Dehydration of Primary Carboxamides to Nitriles by Silyl Sulphonyl Polyphosphates

A new dehydration procedure is described for the conversion of aryl, aralkyl and aliphatic carboxamides to nitriles in high yields under mild conditions using silyl sulphonyl polyphosphates.     

A new one-pot neat synthesis of 1,2,4-triazol-3-ones through 4-（N,N-dimethylamino） pyridine （DMAP） catalyzed cyclocondensation of ethyl carbazate with aryl nitriles

A new one-pot neat synthesis of some 5-aryl-2,4-dihydro-3H- 1,2,4-triazol-3-ones through cyclocondensation of ethyl carbazate with aryl nitriles catalyzed by DMAP as an efficient and basic nucleophilic catalyst is described.     

A new one-pot neat synthesis of 1,2,4-triazol-3-ones through 4-(N, N-dimethylamino) pyridine (DMAP) catalyzed cyclocondensation of ethyl carbazate with aryl nitriles

A new one-pot neat synthesis of some 5-aryl-2,4-dihydro-3H-1,2,4-triazol-3-ones through cyclocondensation of ethyl carbazate with aryl nitriles catalyzed by DMAP as an efficient and basic nucleophilic catalyst is described.     

An improved palladium(II)-catalyzed method for the synthesis of aryl ketones from aryl carboxylic acids and organonitriles

A palladium(II)-catalyzed decarboxylative protocol for the synthesis of aryl ketones has been developed. The addition of TFA was shown to improve the reaction yield and employing THF as solvent enabled the use of solid nitriles and in only a small excess. Using this method, five different benzoic acids reacted with a wide range of nitriles to produce 29 diverse (hetero)aryl ketone derivatives in up to 94% yield.     

Cu(OTf)2-catalyzed synthesis of highly substituted 1-methoxy imidazoles via (3 + 2) cycloaddition between imino carbenoids and nitriles

A Cu(OTf)₂-catalyzed simple synthetic approach for highly substituted 1-alkoxy imidazole has been described. This protocol involves (3 + 2) cycloaddition of oximino carbenoids with organo nitriles. This method has wide substrate scope and tolerates alkyl, aryl, substituted aryl, vinyl, and ester nitriles.     

Transformations of Aryl Ketones via Ligand-Promoted C−C Bond Activation

The coupling of aromatic electrophiles (aryl halides, aryl ethers, aryl acids, aryl nitriles etc.) with nucleophiles is a core methodology for the synthesis of aryl compounds. Transformations of aryl ketones in an analogous manner via carbon–carbon bond activation could greatly expand the toolbox for the synthesis of aryl compounds due to the abundance of aryl ketones. An exploratory study of this approach is typically based on carbon–carbon cleavage triggered by ring-strain release and chelation assistance, and the products are also limited to a specific structural motif. Here we report a ligand-promoted β-carbon elimination strategy to activate the carbon–carbon bonds, which results in a range of transformations of aryl ketones, leading to useful aryl borates, and also to biaryls, aryl nitriles, and aryl alkenes. The use of a pyridine-oxazoline ligand is crucial for this catalytic transformation. A gram-scale borylation reaction of an aryl ketone via a simple one-pot operation is reported. The potential utility of this strategy is also demonstrated by the late-stage diversification of drug molecules probenecid, adapalene, and desoxyestrone, the fragrance tonalid as well as the natural product apocynin.     

Rapid cyanation of aryl iodides in water using microwave promotion

We show that using water in conjunction with microwave heating it is possible to prepare aryl nitriles from the corresponding aryl iodides rapidly and in high yield without the need for a palladium catalyst.